Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet.
Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
Rheumatology (Oxford). 2022 Oct 6;61(10):4145-4154. doi: 10.1093/rheumatology/keac003.
To determine the prevalence and associations of autoantibodies targeting a muscle-specific autoantigen, four-and-a-half-LIM-domain 1 (FHL1), in South Australian patients with histologically-confirmed idiopathic inflammatory myopathies (IIM) and in patients with SSc.
Sera from patients with IIM (n = 267) from the South Australian Myositis Database (SAMD), SSc (n = 174) from the Australian Scleroderma Cohort Study (ASCS) and healthy controls (HC, n = 100) were analysed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA).
Autoantibodies to FHL1 were more frequent in patients with IIM (37/267, 13.8%) compared with SSc (12/174, 7%) (P < 0.02) and HC (2/100, 2%) (P < 0.001). The most common IIM subtypes among FHL1+ IIM patients were (32%) and IBM (2/37, 32%). No statistically significant differences in muscular or extra-muscular manifestations of IIM were found when comparing patients who were anti-FHL1+ with their anti-FHL1- counterparts. In 29/37 (78%) anti-FHL1+ patients, no myositis-specific autoantibodies (MSA) were present. In FHL1+ muscle biopsies, there was less frequent infiltration by CD45+ cells (P = 0.04). There was a trend for HLA alleles DRB107 and DRB115 to be more frequent in anti-FHL1+ compared with anti-FHL1- patients (9/25 vs 19/113, P = 0.09 and 8/25 vs 15/114, P = 0.09, respectively).
We report a substantial prevalence (13.8%) of anti-FHL1 autoantibodies in a large cohort of patients with histologically confirmed IIM; 75% of these cases did not have a detectable myositis-specific autoantibody. Anti-FHL1 autoantibodies were also detected in a subgroup of patients with SSc (7%), indicating that anti-FHL1 autoantibodies may not be myositis-specific. The trend towards an HLA-DR association might indicate a specific immune response to the FHL1 protein.
确定在南澳大利亚经组织学证实的特发性炎性肌病（IIM）患者和系统性硬化症（SSc）患者中，针对肌肉特异性自身抗原的自身抗体，即四半 LIM 结构域 1（FHL1）的患病率及其相关性。
通过酶联免疫吸附试验（ELISA）分析来自南澳大利亚肌炎数据库（SAMD）的 267 例 IIM 患者（n=267）、来自澳大利亚硬皮病队列研究（ASCS）的 174 例 SSc 患者（n=174）和 100 名健康对照者（HC，n=100）的血清中针对 FHL1 的自身抗体。
与 SSc（12/174，7%）（P<0.02）和 HC（2/100，2%）（P<0.001）相比，FHL1 阳性的 IIM 患者（37/267，13.8%）中抗 FHL1 抗体更为常见。在 FHL1+IIM 患者中最常见的 IIM 亚型为（32%）和 IBM（2/37，32%）。与 FHL1 阴性的患者相比，FHL1+患者的 IIM 的肌肉或肌肉外表现无统计学差异。在 29/37（78%）的 FHL1+患者中，不存在肌炎特异性自身抗体（MSA）。在 FHL1+的肌肉活检中，CD45+细胞浸润的频率较低（P=0.04）。与 FHL1 阴性患者相比，HLA 等位基因 DRB107 和 DRB115 在 FHL1+患者中更为常见（9/25 比 19/113，P=0.09 和 8/25 比 15/114，P=0.09）。
我们报告了在一组经组织学证实的大型 IIM 患者中，抗 FHL1 自身抗体的大量患病率（13.8%）；其中 75%的病例未检测到肌炎特异性自身抗体。抗 FHL1 自身抗体也在一组 SSc 患者（7%）中被检测到，这表明抗 FHL1 自身抗体可能不是肌炎特异性的。与 HLA-DR 相关的趋势可能表明对 FHL1 蛋白的特定免疫反应。
